Journal
IMMUNITY
Volume 49, Issue 1, Pages 120-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2018.06.007
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Funding
- ERC [PREG-LAB 647696]
- AXA Chair Translational Immunology
- Agence Nationale de la Recherche [ANR-16-CE18-0007-01]
- Chair of Excellence (Universite Sorbonne Paris Cite)
- Infect-ERA project ABIR [031A403]
- Deutsche Forschungsgemeinschaft [TRR130, FI 1238/1-2]
- JSPS KAKENHI [26293062, 17H05790]
- German Ministry for Education and Research BMBF [01KU1216F]
- Vietnam Ministry of Education and Training [322, 911]
- Grants-in-Aid for Scientific Research [17H05790, 26293062] Funding Source: KAKEN
- Agence Nationale de la Recherche (ANR) [ANR-16-CE18-0007] Funding Source: Agence Nationale de la Recherche (ANR)
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B lymphocytes can suppress immunity through interleukin (IL)-10 production in infectious, autoimmune, and malignant diseases. Here, we have identified a natural plasma cell subset that distinctively expresses the inhibitory receptor LAG-3 and mediates this function in vivo. These plasma cells also express the inhibitory receptors CD200, PD-L1, and PD-L2. They develop from various B cell subsets in a B cell receptor (BCR)-dependent manner independently of microbiota in naive mice. After challenge they upregulate IL-10 expression via a Toll-like receptor-driven mechanism within hours and without proliferating. This function is associated with a unique transcriptome and epigenome, including the lowest amount of DNA methylation at the Il10 locus compared to other B cell subsets. Their augmented accumulation in naive mutant mice with increased BCR signaling correlates with the inhibition of memory T cell formation and vaccine efficacy after challenge. These natural regulatory plasma cells may be of broad relevance for disease intervention.
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